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Gaucher disease
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Gaucher disease was the first lysosomal storage disease for which this approach became available. The major breakthrough in permitting successful therapy was the recognition that lipid-laden macrophages have a mannose receptor [87]; modifying the glycoprotein glucocerebrosidase to expose a terminal mannose permits the enzyme to attach to and be incorporated into the macrophage [48]. A modified form of the enzyme purified from human placenta was approved for treatment in 1991 under the name Ceredase (algucerase), and then in 1994, a form of human glucocerebrosidase produced in cultured Chinese hamster ovary cells was approved under the name Cerezyme (imiglucerase). This has largely replaced alglucerase. Another form, produced in human fibroblasts, was approved in 2010 under the name VPRIV (velaglucerase).
Biotechnology products and indications I. Proteins
Published in Ronald P. Evens, Biotechnology, 2020
Protein enzymes include 31 products, as listed in Table 8.3. The first protein enzyme developed in the late 1980s was alteplase (Activase®), a thrombolytic agent used to minimize complications owing to blood coagulation in acute myocardial infarction. Two further enzymes that were molecularly engineered from alteplase were developed for similar indications. The cardiovascular indications related to thrombolysis have expanded to seven, including acute myocardial infarction, pulmonary embolism, stroke, percutaneous angioplasty, arterial vessel stenting, unstable angina, and acute coronary syndromes with or without unstable angina. A unique enzyme was discovered for cystic fibrosis, dornase alfa, which is the enzyme deficiency responsible for the etiology of this disastrous respiratory disease. Cystic fibrotic patients experience prevention of breakdown of DNA from degrading cells in the lungs, causing sludging of alveolar secretions and very poor lung function. This enzyme was the first protein administered by inhalation, given the nature of the disease being a protein deficiency in the alveoli of lungs. A family of rare single-enzyme deficiencies causes life-ending diseases often in childhood or adolescence, involving multiple organ system disruption (blood, liver, and nervous system). Fifteen such enzyme deficiencies have the replacement enzyme commercially available for 12 diseases, that is, Batten’s, Fabry’s, Gaucher’s, Hunter’s, Hurler’s, Morquio A, Pompe’s, Severe compromised immune disease, Sly, and Maroteaux-Lamy, many of which are specific mucopolysaccharidoses, plus the two diseases with hypophosphatemia and lysosomal acid lipase. Novel rDNA technologies were used primarily to create these replacement enzymes, mitigating the diseases; plus, a gene-activated process was used for a recombinant protein (velaglucerase) and a plant host cell for rDNA for taliglucerase, both products are used in Gaucher’s disease. Two enzymes are available for uric acid abnormalities. Gout is treated with pegloticase. Also, a key enzyme is responsible for uric acid metabolism, principal to the eradication of excess nucleic acid material from dying cells especially in cancers; its deficiency leads to hyperuricemia, and is correctable with the enzyme product rasburicase. Other quite variable and distinct conditions treated with enzyme therapies are acute lymphoblastic leukemia, primary immunodeficiency, Dupuytren’s contracture, methotrexate toxicity, phenylketonuria, and vitreomacular adhesion. Hypodermoclysis (enhancing concurrent drug absorption) involves one enzyme product, Hylenex.
The budget impact of enzyme replacement therapy in type 1 Gaucher disease in the United States
Published in Journal of Medical Economics, 2022
Sepehr Farahbakhshian, Timothy J. Inocencio, Gregory Poorman, Ekaterina Wright, Ravi Ramesh Pathak, Michael Bullano
Early treatment of GD1 with ERT during childhood can potentially prevent some complications of GD, including progression of irreversible skeletal manifestations. Results from a long-term, phase 3 extension study enrolling patients who were treatment naïve before initiating velaglucerase alfa therapy showed continued improvement in signs and symptoms of GD1 in patients who received more than 2 years of therapy13,14. To understand the economic value of velaglucerase alfa in the treatment of GD1, a budget impact model (BIM) was developed from a United States (US) payer perspective.
Pharmacological treatment of pediatric Gaucher disease
Published in Expert Review of Clinical Pharmacology, 2018
Punita Gupta, Gregory Pastores
The results of the three Phase 3 clinical trials and extension trial (ClinicalTrials.gov identifier NCT00635427) revealed a good safety profile and efficacy data that corroborated the long-term (7 years) experience from the seminal Phase 1/2 trial. Velaglucerase alfa has been approved for commercial distribution since 2010 and is currently used by more than 1500 patients in more than 40 countries.